Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry.

Pulmonary hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce. We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000-2017 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer term outcomes in survivors to hospital discharge. 242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons, respectively. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II (Acute Physiology and Chronic Health Evaluation) score, age and lactate, and lower oxygen saturation measure by pulse oximetry/inspiratory oxygen fraction (S pO2 /F iO2 ) ratio, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (oxygen (S pO2 /F iO2 ) ≤185; platelets ≤196×109·L-1; age ≥37.5 years; lactate ≥2.45 mmol·L-1; sodium ≤130.5 mmol·L-1), identified medical patients at increasing risk of hospital mortality. One (11%) out of nine patients who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge. These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation.

Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension.

Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension (PAH), but limited data exist on the routine use of maximal exercise testing.Objectives: This study evaluates a simple-to-perform maximal test (the incremental shuttle walking test) and its use in risk stratification in PAH.Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) registry (2001-2018). Thresholds for levels of risk were identified at baseline and tested at follow-up, and their incorporation into current risk stratification approaches was assessed.Results: Of 4,524 treatment-naive patients with pulmonary hypertension who underwent maximal exercise testing, 1,847 patients had PAH. A stepwise reduction in 1-year mortality was seen between levels 1 (≤30 m; 32% mortality) and 7 (340-420 m; 1% mortality) with no mortality for levels 8-12 (≥430 m) in idiopathic and connective tissue disease-related PAH. Thresholds derived at baseline of ≤180 m (>10%; high risk), 190-330 m (5-10%; intermediate risk), and ≥340 m (<5%; low risk of 1-yr mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) 2.0 risk score calculator and French low-risk approach to risk stratification, and distinct categories of risk remained.Conclusions: We have demonstrated that maximal exercise testing in PAH stratifies mortality risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute walking test, combining some of the advantages of maximal exercise testing and maintaining the simplicity of a simple-to-perform field test.

Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry.

BACKGROUND AND OBJECTIVE: There are limited data regarding patients with PAPVD with suspected and diagnosed PH. METHODS: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry. RESULTS: Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty-seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV-ASD had a significantly larger RV area, pulmonary artery and L-R shunt and a higher % predicted DLCO (all P < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein. CONCLUSION: Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross-sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L-R shunt are higher in patients with an associated SV-ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.

Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension.

There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH).Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAHno-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAHmild-LD (n=190).Survival was significantly better in IPAHno-LD than in IPAHmild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p<0.0001). In the combined group of IPAHno-LD and IPAHmild-LD, independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide (D LCO), lower exercise capacity and a diagnosis of IPAHmild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAHno-LD, but not IPAHmild-LD A proportion of patients with IPAHno-LD had a D LCO <45%; these patients had poorer survival than patients with D LCO ≥45%, although they demonstrated improved exercise capacity following treatment.The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced D LCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required.

Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality.Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making.Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort.Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality.Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.

The incremental shuttle walk test predicts mortality in non-group 1 pulmonary hypertension: results from the ASPIRE Registry.

Pulmonary hypertension (PH) is classified into five groups based on disease etiology but there is only limited information on the prognostic value of exercise testing in non-group 1 PH. In group 1 PH, the incremental shuttle walking test (ISWT) distance has been shown to correlate with pulmonary hemodynamics and predict survival without a ceiling effect. This study assessed the ISWT in non-group 1 PH. Data were retrieved from the ASPIRE Registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) for consecutive patients diagnosed with PH. Patients were required to have been systematically assessed as group 2-5 PH and to have a baseline ISWT within three months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). A total of 479 patients with non-group 1 PH were identified. ISWD and ISWD%pred correlated significantly with symptoms and hemodynamic severity. ISWD and ISWD%pred predicted survival with no ceiling effect. The test was prognostic in groups 2, 3, and 4. ISWD and ISWD%pred and change in ISWD and ISWD%pred at one year were all significant predictors of outcome. In patients with non-group 1 PH the ISWT is a simple non-invasive test that is easy to perform, is predictive of survival at baseline and follow-up, reflects change, and can be used in the assessment of PH of any etiology.

The patient experience of pulmonary hypertension: a large cross-sectional study of UK patients.

BACKGROUND: Pulmonary Hypertension Association UK (PHA-UK) is the only charity in the UK especially for people affected by pulmonary hypertension (PH). To better understand the impact of PH on patients and carers beyond clinical symptoms, the PHA-UK carried out a cross-sectional survey on the effect of PH on daily living, along with a follow-up survey assessing the financial impact of PH. METHODS: This is a descriptive cross-sectional survey of adult patients with PH in the UK. A quantitative survey of four key topics (time to diagnosis, quality of life [QoL], financial impact and specialist treatment), was made available to PHA-UK members and patients on PH therapy, with a follow-up financial impact survey sent to those responders who agreed to be contacted further. Data collection was carried out in January and February 2017 for the main survey, and November and December 2017 for the financial impact survey. RESULTS: The main survey was completed by 567 individuals, and the financial follow-up survey by 171. Mean age of responders was 69 ± 17 years with 70% female. 60% of respondents said PH had a major impact on their QoL, with 45% reporting that treatment and management improves their QoL 'a lot'. The time between first experiencing symptoms and diagnosis was ≥1 year for 48% of patients, with 40% seeing 4+ doctors before diagnosis. 63% of patients reported financial worries. Patients in part-time and full-time work reported the greatest financial burden, with a 13 and 33% fall in monthly income respectively. Patients had positive experiences of treatment in specialist centres, with 62% rating their care 'excellent', and 92% saying they preferred travelling to a specialist centre rather than seeing a local non-specialist. CONCLUSIONS: This study reports the largest UK survey exploring issues affecting patients with PH. The study shows that despite the availability of new therapies, patients are still experiencing delays prior to diagnosis, and experiencing both emotional and financial impacts from the disease. By identifying the areas patients find most important in their treatment, this research can inform future care policies and long-term management to support patients living with PH and their families.

Incremental Shuttle Walking Test Distance Is Reduced in Patients With Pulmonary Hypertension in World Health Organisation Functional Class I.

Background: There is increasing interest in screening for and diagnosing pulmonary hypertension earlier in the course of disease. However, there is limited data on cardiopulmonary abnormalities in patients with pulmonary hypertension newly diagnosed in World Health Organization Function Class (WHO FC) I. Methods: Data were retrieved from the ASPIRE registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral center) for consecutive treatment naïve patients diagnosed with pulmonary hypertension by cardiac catheterization between 2001 and 2010 who underwent incremental shuttle walk exercise testing. Results: Eight hundred and ninety-five patients were diagnosed with Group 1-5 pulmonary hypertension. Despite the absence of symptoms, patients in WHO FC I (n = 9) had a significant reduction in exercise capacity (Incremental shuttle walk distance percent predicted (ISWD%pred) 65 ± 13%, Z score -1.77 ± 1.05), and modest pulmonary hypertension with a median (interquartile range) pulmonary artery pressure 31(20) mmHg and pulmonary vascular resistance 2.1(8.2) Wood Units, despite a normal diffusion of carbon monoxide adjusted for age and sex (DLco)%pred 99 ± 40%. Compared to patients in WHO FC I, patients in WHO FC II (n = 162) had a lower ISWD%pred 43 ± 22 and lower DLco%pred 65 ± 21%. Conclusion: Our results demonstrate that patients with newly diagnosed pulmonary hypertension with no or minimal symptomatic limitation have a significant reduction of exercise capacity.

The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.

Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH.Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014.Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%) versus technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery.Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients.

Incremental shuttle walk test distance and autonomic dysfunction predict survival in pulmonary arterial hypertension.

BACKGROUND: To ensure effective monitoring of pulmonary arterial hypertension (PAH), a simple, reliable assessment of exercise capacity applicable over a range of disease severity is needed. The aim of this study was to assess the ability of the incremental shuttle walk test (ISWT) to correlate with disease severity, measure sensitivity to change, and predict survival in PAH. METHODS: We enrolled 418 treatment-naïve patients with PAH with baseline ISWT within 3 months of cardiac catheterization. Clinical validity and prognostic value of ISWT distance were assessed at baseline and 1 year. RESULTS: ISWT distance was found to correlate at baseline with World Health Organization functional class, Borg score, and hemodynamics without a ceiling effect (all p < 0.001). Walking distance at baseline and after treatment predicted survival; the area under the receiver operating characteristic curve for ability of ISWT distance to predict mortality was 0.655 (95% confidence interval 0.553-0.757; p = 0.004) at baseline and 0.737 (95% confidence interval 0.643-0.827; p < 0.001) at 1 year after initiation of treatment. Change in ISWT distance also predicted survival (p = 0.04). Heart rate (HR) and systolic blood pressure (SBP) parameters reflecting autonomic response to exercise (highest HR, change in HR, HR recovery at 1 minute >18 beats/min, highest SBP, change in SBP, and 3-minute SBP ratio) were significant predictors of survival (all p < 0.05). CONCLUSIONS: In patients with PAH, the ISWT is simple to perform, allows assessment of maximal exercise capacity, is sensitive to treatment effect, predicts outcome, and has no ceiling effect. Also, measures of autonomic function made post-exercise predict survival in PAH.

Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes.

BACKGROUND: Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. METHODS: Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. RESULTS: Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P < .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP = 0.61 sPAP + 2 mm Hg). The relationship in SSc-PAH was similar: mPAP = 0.58 sPAP + 2 mm Hg (P value for difference with IPAH = 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. CONCLUSIONS: The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

Long-term outcomes of domiciliary intravenous iloprost in idiopathic and connective tissue disease-associated pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: There are few published data on the efficacy of i.v. iloprost in pulmonary arterial hypertension (PAH). We present long-term outcomes in PAH patients receiving i.v. iloprost in a large UK referral centre. METHODS: Eighty patients with idiopathic PAH (iPAH, n = 46) or PAH associated with connective tissue disease (CTD-PAH, n = 34) were identified as receiving domiciliary i.v. iloprost between January 1999 and April 2015. Baseline characteristics, doses achieved, functional class at follow-up and survival data were retrieved from hospital databases. RESULTS: Median maximum dose achieved was 4.6 ng/kg/min in the iPAH group and 5.0 ng/kg/min in CTD-PAH patients. Exercise capacity significantly improved in the first 6 months of therapy in IPAH patients. Overall 1-, 3- and 5-year survival was 78%, 64% and 52% in iPAH (P = 0.002) and 64%, 26% and 21% in CTD-PAH. Independent predictors of survival were age and exercise capacity. CONCLUSION: We report improved survival to that previously reported in iPAH patients treated with domiciliary i.v. iloprost. This may be in part related to higher administered doses. Patients with CTD-PAH had poorer survival, reinforcing the need for early transplantation referral in suitable patients.

Pulmonary arterial hypertension associated with congenital heart disease: Comparison of clinical and anatomic-pathophysiologic classification.

BACKGROUND: Between 5% and 10% of patients with congenital heart disease (CHD) develop pulmonary arterial hypertension (PAH-CHD). Patients can be classified using either a clinical or anatomic-pathophysiologic system. No study has previously utilized both systems in a large cohort of patients. METHODS: Two hundred forty consecutive PAH-CHD patients diagnosed at a pulmonary hypertension referral center during 1995 to 2014 were identified from our unit database. Baseline characteristics, treatment and survival data were retrieved and survival analyses was performed. RESULTS: Both systems identified clear differences in baseline characteristics between subgroups. The anatomic-pathophysiologic system identified patients with post-tricuspid defects as having superior survival from point of referral to those with pre-tricuspid or complex defects (p < 0.05). Survival from point of referral was, however, not significantly different when patients were grouped using the clinical classification, although survival in all 4 groups was superior to that of 175 patients with idiopathic pulmonary arterial hypertension. Older age and higher creatinine, lower transfer factor of the lung for DLCO percent predicted and FEV1 percent predicted were independent adverse prognostic factors. CONCLUSION: Both PAH-CHD classification systems identified groups of patients distinct in terms of baseline characteristics. In our cohort, however, only the anatomic-pathophysiologic classification identified significantly different survival from point of referral. The presence of adverse prognostic markers may be useful in identifying patients requiring more aggressive pulmonary vascular therapy.

A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis.

A major problem faced by patients with amyotrophic lateral sclerosis (ALS) in respiratory failure is the inability to cough effectively. Forty eligible ALS patients were randomized to the breath-stacking technique using a lung volume recruitment bag (n = 21) or mechanical insufflator-exsufflator MI-E (n = 19) and followed up at three-monthly intervals for at least 12 months or until death. Results showed that there were 13 episodes of chest infection in the breath-stacking group and 19 episodes in the MI-E group (p = 0.92), requiring 90 and 95 days of antibiotics, respectively (p = 0.34). The mean duration of symptoms per chest infection was 6.9 days in the breath-stacking group and 3.9 days in MI-E group (p = 0.16). There were six episodes of hospitalization in each group (p = 0.64). The chance of hospitalization, in the event of a chest infection, was 0.46 in the breath-stacking group and 0.31 in MI-E group (p = 0.47). Median survival in the breath-stacking group was 535 days and 266 days in the MI-E group (p = 0.34). The QoL was maintained above 75% of baseline for a median of 329 days in the breath-stacking group and 205 days in the MI-E group (p = 0.41). In conclusion, lack of statistically significant differences due to sub-optimal power and confounders precludes a definitive conclusion with respect to the relative efficacy of one cough augmentation technique over the other. This study however, provides useful lessons and informative data, needed to strengthen the power calculation, inclusion criteria and randomization factors for a large scale definitive trial. Until such a definitive trial can be undertaken, we recommend the breath-stacking technique as a low-cost, first-line intervention for volume recruitment and cough augmentation in patients with ALS who meet the criteria for intervention with non-invasive ventilation.

Effects of a pragmatic lifestyle intervention for reducing body mass in obese adults with obstructive sleep apnoea: a randomised controlled trial.

This study investigated the effects of a pragmatic lifestyle intervention in obese adults with continuous positive airway pressure-treated obstructive sleep apnoea hypopnoea syndrome (OSAHS). Sixty patients were randomised 1 : 1 to either a 12-week lifestyle intervention or an advice-only control group. The intervention involved supervised exercise sessions, dietary advice, and the promotion of lifestyle behaviour change using cognitive-behavioural techniques. Outcomes were assessed at baseline (week 0), intervention end-point (week 13), and follow-up (week 26). The primary outcome was 13-week change in body mass. Secondary outcomes included anthropometry, blood-borne biomarkers, exercise capacity, and health-related quality of life. At end-point, the intervention group exhibited small reductions in body mass (-1.8 [-3.0, -0.5] kg; P = 0.007) and body fat percentage (-1 [-2, 0]%; P = 0.044) and moderate improvements in C-reactive protein (-1.3 [-2.4, -0.2] mg·L(-1); P = 0.028) and exercise capacity (95 [50, 139] m; P < 0.001). At follow-up, changes in body mass (-2.0 [-3.5, -0.5] kg; P = 0.010), body fat percentage (-1 [-2, 0]%; P = 0.033), and C-reactive protein (-1.3 [-2.5, -0.1] mg·L(-1); P = 0.037) were maintained and exercise capacity was further improved (132 [90, 175] m; P < 0.001). This trial is registered with ClinicalTrials.gov NCT01546792.

Ambrisentan therapy in pulmonary hypertension: clinical use and tolerability in a referral centre.

INTRODUCTION: Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH). METHODS: All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases. RESULTS: 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (<1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy. CONCLUSION: Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.

Incremental shuttle walk test in the assessment of patients with obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome is associated independently with an increase in cardiovascular risk factors and is associated with self-reported lack of exercise. We aimed to investigate the utility of the incremental shuttle walk test in routine clinical practice to monitor physical capacity of patients with obstructive sleep apnea-hypopnea syndrome and explore whether continuous positive airway pressure therapy alters exercise capacity. Participants with symptomatic moderate/severe obstructive sleep apnea-hypopnea syndrome attending for a trial of continuous positive airway pressure therapy completed questionnaires assessing sleepiness and physical activity and underwent an incremental shuttle walk test. Subjects compliant or partially compliant with continuous positive airway pressure therapy underwent reassessment at 2 weeks, 3 months and 6 months post-initiation of therapy. Participants unable to tolerate continuous positive airway pressure therapy completed a single reassessment 6 months after their initial visit. Continuous positive airway pressure therapy resulted in an increased distance walked during the incremental shuttle walk test. Improvements in cardiovascular responses to exercise were identified. Compliant patients reported increased daily activity. The incremental shuttle walk test is a simple, reproducible and safe test that is responsive to continuous positive airway pressure treatment. Our findings support the use of the incremental shuttle walk test for monitoring the effects of continuous positive airway pressure treatment and may suggest its use in rehabilitation programmes designed to reduce obesity and cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome.

Pulmonary hypertension in COPD: results from the ASPIRE registry.

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.

Using transcutaneous carbon dioxide monitor (TOSCA 500) to detect respiratory failure in patients with amyotrophic lateral sclerosis: a validation study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, respiratory failure being the commonest cause of death. Quality of life and survival can be improved by supporting respiratory function with non-invasive ventilation. Transcutaneous carbon dioxide monitoring is a non-invasive method of measuring arterial carbon dioxide levels enabling simple and efficient screening for respiratory failure. The aim of this study was to validate the accuracy of carbon dioxide level recorded transcutaneously with a TOSCA 500 monitor. It is a prospective, observational study of 40 consecutive patients with ALS, recruited from a specialist ALS clinic. The partial pressure of carbon dioxide (PCO(2)) in each patient was determined by both transcutaneous monitoring and by an arterialized ear lobe capillary blood sample. The carbon dioxide (CO(2)) levels obtained with these two methods were compared by Bland-Altman analysis. The results showed that the mean difference between arterialized and transcutaneous readings was - 0.083 kPa (SD 0.318). The Bland-Altman limits of agreement ranged from 0.553 to - 0.719 kPa. The difference was < 0.5 kPa in 90% of the recordings. Four of the 40 measurements had a difference of > 0.5 kPa, with a maximum recorded difference of 0.95 kPa. In conclusion, non-invasive carbon dioxide monitoring using a TOSCA monitor is a useful clinical tool in neurology practice. Users should be aware of the possibility of occasional inaccurate readings. A clinically unexpected or incompatible reading should be verified with a blood gas analysis, especially when a decision to provide ventilatory support is required.

Chronic obstructive pulmonary disease among residents of an historically industrialised area.

OBJECTIVE: To assess the contribution of workplace exposures to chronic obstructive pulmonary disease (COPD) risk in a community with a heavy burden of past industrial employment. METHODS: A random population sample of Sheffield, U.K. residents aged over 55 years (n=4000), enriched with a hospital-based supplemental sample (n=209), was approached for study. A comprehensive self-completed questionnaire elicited physician-made diagnoses, current symptoms, and past workplace exposures. The latter were defined in three ways: self-reported exposure to vapours, gases, dusts and fumes (VGDF); response to a specific exposure checklist; and through a job exposure matrix (JEM) assigning exposure risk likelihood based on job history independent of respondent-reported exposure. A subset of the study group underwent lung function testing. Population attributable risk fractions (PAR%), adjusted for age, sex and smoking, were calculated for association between workplace exposure and COPD. RESULTS: 2001 (50%) questionnaires were returned from the general population sample and 60 (29%) by the hospital supplement. Among 1754 with complete occupational data, any past occupational exposure to VGDF carried an adjusted excess risk for report of a physician's diagnosis of COPD, emphysema, or chronic bronchitis (ORs 3.9; 95% CI 2.7 to 5.8), with a corresponding PAR% value of 58.7% (95% CI 45.6% to 68.7%). The PAR% estimate based on JEM exposure was 31%. From within the subgroup of 571 that underwent lung function testing, VGDF exposure was associated with a PAR% of 20.0% (95% CI -7.2 to 40.3%) for Global initiative for chronic obstructive lung disease (GOLD) 1 (or greater) level of COPD. CONCLUSION: This heavy industrial community-based population study has confirmed significant associations between reported COPD and both generic VGDF and JEM-defined exposures. This study supports the predominantly international evidence-based notion that workplace conditions are important when considering the current and future respiratory health of the workforce.